COMMITTEE ON HERBAL MEDICINAL PRODUCTS (HMPC) FINAL COMMUNITY HERBAL MONOGRAPH ON HYPERICUM PERFORATUM L., HERBA (TRADITIONAL USE)

Transcription

1 European Medicines Agency Evaluation of Medicines for Human Use London, 12 November 2009 Doc. Ref.: EMEA/HMPC/745582/2009 COMMITTEE ON HERBAL MEDICINAL PRODUCTS (HMPC) FINAL COMMUNITY HERBAL MONOGRAPH ON HYPERICUM PERFORATUM L., HERBA (TRADITIONAL USE) DISCUSSION IN WORKING PARTY ON COMMUNITY MONOGRAPHS AND COMMUNITY LIST (MLWP) ADOPTION BY HMPC FOR RELEASE FOR CONSULTATION END OF CONSULTATION (DEADLINE FOR COMMENTS) REDISCUSSION IN WORKING PARTY ON COMMUNITY MONOGRAPHS AND COMMUNITY LIST (MLWP) March 2008 May 2008 July 2008 September 2008 November November February 2009 July 2009 September 2009 November 2009 ADOPTION BY HMPC 12 November 2009 KEYWORDS Herbal medicinal products; HMPC; Community herbal monographs; traditional use; Hypericum perforatum L.; Hyperici herba; St. John s wort 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) Fax (44-20) mail@emea.europa.eu European Medicines Agency, Reproduction is authorised provided the source is acknowledged

2 COMMUNITY HERBAL MONOGRAPH ON HYPERICUM PERFORATUM L., HERBA (TRADITIONAL USE) 1. NAME OF THE MEDICINAL PRODUCT To be specified for the individual finished product. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1, 2 With regard to the marketing authorisation application of Article 10(a) of Directive 2001/83/EC as amended See document EMEA/HMPC/101304/2008 With regard to the registration application of Article 16d(1) of Directive 2001/83/EC as amended Hypericum perforatum L., herba (St. John s Wort) i) Herbal substance Not applicable ii) Herbal preparations 3 A) Dry extract (DER 4-7:1), extraction solvent ethanol 38% (m/m) B) Liquid extract (DER 1:4-20), extraction solvent vegetable oil 4 C) Liquid extract (DER 1: 13), extraction solvent maize oil or other suitable vegetable oil D) Tincture (Ratio of herbal substance to extraction solvent 1:10), extraction solvent ethanol 45-50% (v/v) E) Tincture (Ratio of herbal substance to extraction solvent 1:5), extraction solvent ethanol 50% (v/v) F) Liquid extract (DER 1:2), extraction solvent ethanol 50% (v/v) G) Liquid extract (DER 1:5-7), extraction solvent ethanol 50% (v/v) H) Expressed juice from the fresh herb (DER :1) 5 I) Comminuted herbal substance J) Powdered herbal substance 1 The material complies with the Ph. Eur. monograph (ref. 01/2008:1438) 2 The declaraction of the active substance(s) for an individual finished product should be in accordance with the relevant herbal quality guidance. 3 If relevant, the amount of hyperforin and hypericin should be specified. The daily intake of hyperforin has to be below 1 mg. 4 Preparation: maceration of the fresh or dried herbal substance with vegetable oil over a period of 2 days to several weeks under sun light exposure. 5 Fresh material complies with the Ph. Eur. monograph (ref. 01/2008:1438) when dried. EMEA /9

3 3. PHARMACEUTICAL FORM Comminuted herbal substance as herbal tea for oral use. Herbal preparations A, J in solid dosage forms for oral use. Herbal preparations C, D, E, F, G, H in liquid dosage forms for oral use. Herbal preparations B, D, E, I in liquid or semisolid dosage forms for cutaneous use. The pharmaceutical form should be described by the European Pharmacopoeia full standard term. 4. CLINICAL PARTICULARS 4.1. Therapeutic indications Indication 1 Herbal substance, herbal preparations A, C, D, E, F, G, H, I, J: Traditional herbal medicinal product for the relief of temporary mental exhaustion. Herbal preparations B, D, E, I: Traditional herbal medicinal product for the symptomatic treatment of minor inflammations of the skin (such as sunburn) and as an aid in healing of minor wounds. Indication 3 Herbal preparation I: Traditional herbal medicinal product for the symptomatic relief of mild gastrointestinal discomfort. The product is a traditional herbal medicinal product for use in specified indications exclusively based upon long-standing use. EMEA /9

4 4.2. Posology and method of administration Posology Indication 1 Adults, elderly Herbal preparation A: Single dose: mg Daily dose: mg Herbal preparation C: Single dose: 200 mg Daily dose: 600 mg Herbal preparation D: Single dose: 2-4 ml Daily dose: 6-12 ml Herbal preparation E: Single dose: ml Daily dose: ml Herbal preparation F: Single dose: ml Daily dose: ml Herbal preparation G: Single dose: 1.3 ml Daily dose: 4 ml Herbal preparation H: Single dose: ml Daily dose: ml Herbal preparation I: For tea preparation: Single dose: g Daily dose: 3-6 g Herbal preparation J: Single dose: mg Daily dose: mg Children, adolescents The use in children and adolescents under 18 years of age is not recommended (see section 4.4 Special warnings and precautions for use ). EMEA /9

5 Adolescents, adults, elderly Herbal preparations B, I: Cutaneous administration of the undiluted herbal preparation Herbal preparations D, E: Cutaneous administration of the undiluted or diluted herbal preparation Children The use in children under 12 years of age is not recommended (see section 4.4 Special warnings and precautions for use ). Indication 3 Adults, elderly Herbal preparations I: For tea preparation: Single dose: 2 g Daily dose: 4 g Children, adolescents The use in children and adolescents under 18 years of age is not recommended (see section 4.4 Special warnings and precautions for use ). Duration of use Indication 1 If the symptoms persist longer than 2 weeks during the use of the medicinal product, a doctor or a qualified health care practitioner should be consulted. Indications 2 and 3 If the symptoms persist longer than 1 week during the use of the medicinal product, a doctor or a qualified health care practitioner should be consulted. Method of administration Oral use. Cutaneous use. EMEA /9

6 4.3. Contraindications Hypersensitivity to the active substance Special warnings and precautions for use During the treatment intense UV-exposure should be avoided. Since no sufficient data are available the use in children and adolescents under 18 years of age is not recommended. For tinctures containing ethanol, the appropriate labelling for ethanol, taken from the Guideline on excipients in the label and package leaflet of medicinal products for human use, must be included. During the treatment intense UV-exposure of the respective skin areas should be avoided. Since no data on the safe use in children are available, the use in children under 12 years of age is not recommended. If signs of skin infections are observed, a doctor or a qualified healthcare practitioner should be consulted Interactions with other medicinal products and other forms of interaction In the case of a daily intake of hyperforin less than 1 mg and of a duration of use not longer than 2 weeks (see section 4.2. Posology and method of administration ), no clinically relevant interactions are to be expected. Patients taking other medicines on prescription should consult a doctor or pharmacist before taking Hypericum. EMEA /9

7 None reported Pregnancy and lactation In the absence of sufficient data, the use during pregnancy and lactation is not recommended Effects on ability to drive and use machines No adequate studies on the effect on the ability to drive and use machines have been performed. Not relevant Undesirable effects Gastrointestinal disorders, allergic skin reactions, fatigue and restlessness may occur. The frequency is not known. Fair-skinned individuals may react with intensified sunburn-like symptoms under intense sunlight. If other adverse reactions not mentioned above occur, a doctor or a qualified health care practitioner should be consulted. Skin reactions may occur. The frequency is not known. If other adverse reactions not mentioned above occur, a doctor or a qualified health care practitioner should be consulted. EMEA /9

8 4.9. Overdose After the intake of up to 4.5 g dry extract per day for 2 weeks and additionally 15 g dry extract just before hospitalisation seizures and confusion have been reported. After ingestion of massive overdoses, the patient should be protected from sunlight and other UV-light sources for 1-2 weeks. 5. PHARMACOLOGICAL PROPERTIES 5.1. Pharmacodynamic properties Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended Pharmacokinetic properties Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended Preclinical safety data Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended, unless necessary for the safe use of the product. Studies on acute toxicity and repeated dose toxicity did not show signs of toxic effects. The weak positive results of an ethanolic extract in the AMES-test (Salmonella typhimurium TA 98 and TA 100, with and without metabolic activation) could be assigned to quercetin and are irrelevant to human safety. No signs of mutagenicity could be detected in further in-vitro and in-vivo test systems. Tests on reproductive toxicity revealed equivocal results. Tests on the carcinogenic potential have not been performed. EMEA /9

9 Phototoxicity: After oral application of dosages of 1800 mg of an extract per day for 15 days the skin sensitivy against UVA was increased, and the minimum dose for pigmentation was significantly reduced. In the recommended dosage, no signs of phototoxicity are reported. 6. PHARMACEUTICAL PARTICULARS The amount of hyperforin has to be specified in herbal preparation for oral use. The daily intake of hyperforin has to be below 1 mg. 7. DATE OF COMPILATION/LAST REVISION 12 November 2009 EMEA /9